RASA1/NF1-Mutant Lung Cancer: Racing to the Clinic?
Open accessAbstract
Although mutation of NF1 has been described in non–small cell lung cancer (NSCLC), co-mutation with RASA1, another Ras-GTPase activating protein (RasGAP), defines a novel genetically defined subclass of NSCLC. RASA1/NF1-mutant cell lines are highly sensitive to MEK inhibitors, warranting clinical evaluation of MAPK inhibition in this subclass of patients. Clin Cancer Res; 24(6); 1243–5. ©2018 AACR. See related article by Hayashi et al., p. 1436
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In a separate cohort with acquired EGFR T790M, RB1 and PTEN co-mutations plus MDM2 amplification independently predicted poorer PFS on third-generation EGFR TKIs.
“among patients with acquired EGFRT790M mutation from a distinct cohort, co-mutations in RB1 and PTEN and amplification of MDM2 were independently associated with worse progression-free survival following treatment with 3rd generation EGFR TKIs72, 173.”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [173]
In that same cohort, baseline ERBB2 amplification (4%) also predicted markedly shorter PFS on first-line first- or second-generation EGFR TKIs.
“In a study of 200 EGFR-mutant patients with extensive molecular profiling at baseline, pre-existing MET (present in 2% of cases) or ERBB2 (4% prevalence) amplification were also associated with significantly shorter progression-free survival with first-line 1st or 2nd generation EGFR TKI therapy”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [173]
Among 200 EGFR-mutant patients, baseline MET amplification (2%) predicted markedly shorter PFS on first-line first- or second-generation EGFR TKIs.
“In a study of 200 EGFR-mutant patients with extensive molecular profiling at baseline, pre-existing MET (present in 2% of cases) or ERBB2 (4% prevalence) amplification were also associated with significantly shorter progression-free survival with first-line 1st or 2nd generation EGFR TKI therapy”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [173]
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Cites
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Additional file 1 of Altered expression of ACOX2 in non-small cell lung cancer
Sui, J. S. Y., Martin, P., Keogh, A., Murchan, P., Ryan, L., Nicholson, S. A., Cuffe, S. D., Broin, P. Ó., Finn, S. P., Fitzmaurice, G. J., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20579709
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“In lung adenocarcinomas, the simultaneous inactivation of NF1, RASA1, 395 and PTEN contributes to synergistic oncogenic signaling and tumor development.”
- Authors
- Kitajima, S., & Barbie, D. A.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Barbie, David A.
- Venue
- Clinical Cancer Research
- Published
- 2018-03-14
- Volume
- 24
- Issue
- 6
- Pages
- 1243-1245
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC5856629
- OpenAlex
- W2791729921
- Cited by
- 23
- References
- 5
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 6
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01CA190394)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- RASA1, neurofibromatosis type 1, non-small cell lung cancer, Ras GTPase-activating protein, MEK inhibitors, MAPK inhibition, targeted therapy
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Smoking, p120 GTPase Activating Protein, Protein Kinase Inhibitors
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